Patients with hypertrophic cardiomyopathy (HCM) frequently experience chest pain that occurs with variable threshold of onset and is often prolonged in duration. The study was designed to evaluate the effect of a pharmacologic vasoconstrictor agent, ergonovine, on the cornoary vasculature of patients with HCM. Twenty-three patients with HCM and a history of angina pectoris despite normal epicardial coronary arteries underwent a study of coronary flow, myocardial mechanics, and metabolism. During pacing to an average heart rate of 133,18 of the 23 patients experienced their typical chest pain. During pacing after the administration of ergonovine, 21 of 23 patients experienced chest pain. Despite a significantly higher blood pressure, the coronary blood flow at an average pacing rate of 138 beats/min was significantly lower than during pacing alone to a similar heart rate. There was no epicardial coronary artery narrowing during a repeat coronary arteriography. Thus, peak coronary flow decreases with ergonovine in patients with HCM, probably due to vasoconstriction of a maximally dilated microvascular bed, or vasoconstriction of prearteriolar small coronary arteries. Small vessel coronary vasoconstriction may explain many of the atypical features of angina pectoris in patients with HCM causing pain at rest or during variable levels of effort.